One of the challenges in areas of drug development and drug delivery for treating various human diseases is the lack of understanding of the inherent cellular barriers that restrict the drug efficacy. Another challenge encountered by researchers conducting intracellular trafficking of molecules and their localization in cellular organelles is in the use of fluorescent labels that distort the study results with negative influence of these labels on samples. Further, lack of availability of adequate instrumentation restricts investigators from conducting cutting-edge research at their own institute. As a result they have to ship their materials to institutions/universities which are time-consuming, expensive, and do not give the investigator to know the results quickly. Therefore, continuous expansion of research infrastructure by acquiring appropriate equipment?s will enhance research activities among research investigator and lead to new discoveries. To override some of these limitations, we are requesting funds to purchase the CytoViva 3D Enhanced Darkfield Hyperspectral Microscope for enhancing the research conducted by investigators at the Oklahoma City VA Health Care System. This system offers high signal-to-noise 3D enhanced darkfield optical hyperspectral imaging specifically designed for imaging of label free particles/molecules in label-free or fluorescently labeled live cells and ex-vivo tissue matrices. The unique patented technology of the microscope allows the visualization and monitoring of particles, drugs, biologics, and cells in solution and in translucent matrices (cells, tissues, organisms). Thus, studies investigating binding of material (drug, nanoparticle, cell- particle interaction, antibody binding to cell), receptor-mediated binding and entry into cells (nanoparticles, quantum-dots, virus, bacteria, metals, antibodies) and intracellular localization and trafficking (siRNA, plasmid DNA, nanoparticles, virus, bacteria, spores) via various intracellular organelles can be determined in vitro and in ex-vivo tissue explants with label-free imaging and capture images. The system with the requisite computer software system provides quantitative spectral analysis of biological and non-biological materials imaged. The protocols can be automated giving the user to ?walk-away? from the instrument, and perform other experiments. Most importantly, neither the Oklahoma City VA Health Care System nor the affiliated University of Oklahoma Health Sciences Center (OUHSC) has such an instrument that enables high precision analysis of label-free materials in cells or ex-vivo tissues. Therefore, this is a truly unique and valuable resource justifying it purchase as a resource for investigators to conduct existing and new areas of research at the Oklahoma City VA Health Care System. Availability of this equipment will enhance ongoing studies and establish new areas of research benefitting the men and women serving the military and veterans. The equipment will be used by six-major users and a number of future VA users who have six VA Merit grants funded, three senior career scientist awards, and one career development award funded.